Human stem cells are proving useful in basic research in several ways. They are useful in unraveling the complex molecular pathways governing human differentiation. For example, because ESCs can be stimulated in vitro to produce more differentiated cells, this transition can be studied in greater detail and under better-controlled conditions than it can be in vivo. In the best circumstances, these differentiated cells can be grown as largely homogeneous cell populations, and their gene expression profiles can be compared in detail.Also, stem cell preparations can be used to produce populations of specialized cells that are not easily obtained in other ways. In one case, for example, this approach has provided large quantities of human trophoblast-like cells that have not been previously available.35 In addition, cultures of differentiated cells derived from stem cells could be used to test new drugs and chemical compounds for toxicity and mutagenicity.36As experience with these differentiated derivatives of human ESCs grows, it may become possible to reduce or eliminate the use of live animals in such testing protocols.In the near future, the differentiated state of various human cell types will be characterized not just by a few biological markers, but by the pattern and levels of expression of hundreds or thousands of genes. Integration of this knowledge with the catalog of all human genes produced during the Human Genome Project will gradually give us knowledge of which genes are key regulators of human development and which genes are central to maintaining the stem cell state.37 Increased understanding of the molecular pathways of human cell differentiation should eventually lead to the ability to direct in vitro differentiation along pathways that yield cells useful in medical treatment. In addition, when the normal range of gene expression patterns is known, researchers can then determine which genes are expressed abnormally in various diseases, thus increasing our understanding of and ability to treat these diseases.A group of stem cell researchers has recently outlined a set of important research questions that, once answered, will greatly enhance our understanding of human embryonic stem cells and their potential fates and possible uses.38 They include the following:
What is the most effective way to isolate and grow ESCs?
How is the self-renewal of ESCs regulated?
Are all ESC lines the same?
How can ESCs be genetically altered?
What controls the processes of ESC differentiation?
What new tools are needed to measure ESC differentiation in vitro and in vivo?
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